Quaternary ammonium salts of 20beta-amino-allopregnane-3beta-ol



United States Patent QUATERNARY AMMONIUM SALTS OF 20 3-AMINO-ALLOPREGNANE-IlB-OL Percy George Holton, Mexico City, Mexico,assignor to Syntex S.A., Mexico City, Mexico, a corporation of Mexico NoDrawing. Filed July 6, 1961, Ser. No. 122,084

3 Claims. (Cl. 260-3975) In the above equation Me represents the methylgroup; X may be a number from 3 to 6 inclusive.

The products of the present invention are prepared by the processillustrated by the following equation:

CH; OH;

In the above formulas X has the same meaning as above set forth.

In practicing the process outlined above, the starting compoundallopregnan-BB-ol-ZO-one (I) is conventionally treated withhydroxylamine hydrochloride affording the corresponding oxime (-II)which upon reduction with sodium-ethanol furnishes20fi-amino-allopregnan-3B-ol (III).

This compound is refluxed with formic acid and formaldehyde for a periodof time of the order of 2 hours to give20B-N,Ndimethylaminoallopregnan-Bfl-ol (IV). Upon treatment of thiscompound with a (w-bromoloweralkyl) trirnethyl-ammoniumbromide, in asuitable solvent such as acetonitrile, there is obtained thecorresponding ZOB-N-('N',N'-dimethylaminoloweralkyl) N-methylamino-allopregnan-3,3-ol-bis-methobromide (V).

The following specific examples serve to illustrate but are not intendedto limit the, present invention:

Example I A mixture of 1 g. of a1lopregnan-3B-ol-20-one, 2 g. ofhydroxylamine hydrochloride, and 2 g. of sodium acetate in 200 cc. ofmethanol is heated under reflux for 20 hours. 100 ml. of water wereadded and the mixture was evaporated under reduced pressure until theappearance of crystals. After cooling, the formed crystals were filteredofi? and dried, thus affording the allopregnan- 3 8-01 20-one oxime.

To a refluxing solution of this oxime in 100 cc. of nbutanol were addedportionwise 5 g. of sodium. The resulting solution was diluted with 100cc. of water, acidified with acetic acid and evaporated under reducedpressure until the butanol had been removed. The acidic solution waswashed with ether, made alkaline with a 5% aqueous sodium hydroxidesolution, the liberated product extracted with methylene chloride, theextract washed with water, dried over anhydrous sodium sulfate andevaporated to dryness. Recrystallization from acetone afiorded20fl-amino-allopregnan-3 3-01.

Example II 1 g. of this last steroid was refluxed with 3 cc. of formicacid and 2.5 cc. of 40% formaldehyde for 2 hours. The mixture wasevaporated under reduced pressure, the residue alkalized with sodiumcarbonate solution and the resulting mixture extracted with ether. Theextract was washed with water, dried over sodium sulfate and evaporatedto dryness. Recrystallization from ethanol- Example III A mixture of 1g. of the foregoing compound, 2 g. of

l -bromopropyn-trimethy-l ammonium bromide, and 10 cc. of acetonitrilewas refluxed for 24 hours, then cooled and diluted with ether. Theprecipitate thus formed was collected and rec'rystallized from methanolgiving 205- N-(N,N'-dimethylaminopropyl)N methylaminoallopregnan-3fl-obbis-methobromide.

Example IV 1 g. of 20,8-(N,N-dimethylamino)-al1opregnan-3 9-ol wastreated following the technique described in Example III except that('y-bromo-propyl)-trimethyl-a.mmonium bromide was substituted by(6-bromobutyD-trimethylbenzene afiorded2018-(N,N-dimethy1amino)-5l1opiegnanammonium bromide thus affording20fi-N-(N,N'-dimethylaminobutyl)N-methylamino allopregnan 3,8'ol-bismethobromide.

I claimi 1. A compound of the folio, ng formula:

0H; CH. C|H3 HC-N+(C m rN -CH1 CH3 CH;

wherein X is an integer from 3 to 6.

2. 2013 N -(NZN dimethy-laminopropyl) -N--methylamino-allopregnan-3fl-ol-bis-methobromide.

3. 20B N (N',N'-di-methylaminobutyl)-(N methyl-jamino-allopregnan-Sfi-ol bisemethobromider No references citdl,

1. A COMPOUND OF THE FOLLOWING FORMULA: WHEREIN X IS AN INTEGER FROM 3TO 6.